Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149871 (deep vein thrombosis)
 12,364 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arterial embolism is usually caused by cardiac disease, and atherosclerotic coronary vascular disease is the primary precursor. Other cardiac states, as well as several uncommon causes, are part of the etiologic spectrum. The earliest signs are pain, paresthesias, pallor, and pulselessness. Severe ischemia is indicated by paralysis, a late feature. Arterial embolism and acute thrombosis can be difficult to distinguish, and deep venous thrombosis may also be suspected in the differential diagnosis. To restore arterial flow, anticoagulation treatment with heparin (Lipo-Hepin, Liquaemin) is given and surgical embolectomy is performed. Heparin infusion is continued until the patient is ambulatory, and then warfarin sodium (Coumadin, Panwarfin) is given over the long term. Fibrinolysis has also been used to treat acute arterial occlusion. Complications of embolism must be carefully guarded against, and additional procedures are sometimes necessary.
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PMID:Management of arterial emboli. Gleanings from 20 years of experience. 357 97

Heparin (Lipo-Hepin, Liquaemin Sodium) and warfarin sodium (Coumadin, Panwarfin) are the classic anticoagulants in use for venous thromboembolic disease. They work by modifying the coagulation mechanism, heparin having an immediate effect and warfarin having a more delayed effect. The most common adverse effects of anticoagulation therapy are hemorrhagic complications. Thrombolytic therapy should be considered in all patients with massive pulmonary embolism with hypotension and in patients with deep venous thrombosis in the popliteal area or higher. Such therapy has been shown to help preserve the pulmonary microcirculation after pulmonary embolism and to decrease the incidence of the postthrombotic syndrome following deep venous thrombosis. If certain clinical guidelines are followed rigidly, the incidence of significant bleeding complications is low. Although the use of tissue plasminogen activator in venoocclusive disease has been limited to isolated cases, results have been very promising.
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PMID:Treatment of venous thromboembolic disease. A pragmatic approach to anticoagulation and thrombolysis. 370 54

In a prospective, controlled clinical study prevention of postoperative deep venous thrombosis by low-dose heparin (Heparin Leo 5 000 I.U. subcutaneously twice daily) was compared with graded compression stockings (TED stockings, Kendall Co.). One hundred and twelve patients, admitted during a period of one year for elective major surgery, were allocated to one of the two treatment groups. In order to detect deep venous thrombosis the 99mTc-plasmin test was performed before the operative procedure and again 5 days later. Ninety-seven patients completed the study (45 patients in the heparin group and 52 patients in the stocking group). Venous thromboembolism was detected in 4 patients (8.9%) in the heparin group and in 3 patients (5.8%) in the stocking group (p greater than 0.05). In 6 patients the plasmin test was positive and one patient in the heparin group died following pulmonary embolism. It is concluded that graded compression stockings can be used as an alternative to low-dose heparin for prophylaxis against deep venous thrombosis in elective general surgery.
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PMID:Prevention of postoperative deep venous thrombosis. Low-dose heparin versus graded pressure stockings. 389 94

Heparin sodium is routinely used in the prophylaxis against deep venous thrombosis in medical and surgical patients. While most physicians are aware of heparin-induced thrombocytopenia and skin necrosis, the association of heparin and hyperkalemia is less well recognized. We present four cases in which the use of heparin was associated with hyperkalemia and discuss the pathophysiology. Our findings suggest that hyperkalemia can develop with the use of low-dose heparin, within seven days of initiating heparin therapy, and that patients with diabetes mellitus or chronic renal insufficiency are especially predisposed to this complication.
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PMID:Heparin-induced hyperkalemia. 400 33

In a randomized clinical trial the effect of subcutaneous heparin alone or in combination with dihydroergotamine or sulphinpyrazone in preventing postoperative deep vein thrombosis (DVT) was studied. Sodium heparin (5000 IU) was administered subcutaneously twice daily; dihydroergotamine (1/2 mg) was also administered subcutaneously twice daily, and sulphinpyrazone (400 mg) was administered orally or intravenously twice daily. Administration occurred for at least 7 days. The diagnosis DVT was made with the radiofibrinogen uptake test. 358 patients undergoing major elective abdominal surgery were allocated to three treatment groups: heparin alone (Hep), heparin + dihydroergotamine (DHE-Hep) and heparin + sulphinpyrazone (Sulph-Hep). The frequency of DVT was 14/114 in Hep, 10/115 in DHE-Hep and 20/114 in Sulph-Hep. These differences were not significant. After application of the "logistic regression" procedure of Cox (1) it turned out that the major risk factors for developing DVT were age, sex, weight, type of operation and presence of diabetes mellitus. Also a significant treatment influence was observed (p = 0.001). This treatment effect was most probably due to improvement in the DHE-Hep group. The results in the Sulph-Hep group were not significantly different from those in the Hep group. A risk index was formulated on the basis of the above mentioned risk factors by which the chance of occurrence of DVT during heparin prophylaxis in an individual patient could be predicted. Patients that should receive additional prophylactic treatment can be defined by using this risk index.
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PMID:Prevention of postoperative deep vein thrombosis by a combination of subcutaneous heparin with subcutaneous dihydroergotamine or oral sulphinpyrazone. 408 92

The present trial was designed to comparatively investigate the pharmacokinetic profile and evaluate the apparent bioavailability pattern of three already marketed low molecular mass heparins (LMMHs): dalteparin (Fragmin), nadroparin (Fraxiparin), and enoxaparin (Lovenox) given by subcutaneous route. The study was carried out in 20 healthy young volunteers given, according to a cross over design, a single subcutaneous injection of the doses recommended for the prophylaxis of deep vein thrombosis (commercial preparations, prefilled syringes): dalteparin 2,500 IU (= 2,500 IU anti-Xa), nadroparin 7,500 ICU (= 3,075 IU anti-Xa), enoxaparin 20 mg (= 2,000 IU anti-Xa) and enoxaparin 40 mg (= 4,000 IU anti-Xa). Of the markers used, activated partial thromboplastin time (APTT), thrombin clotting time (TCT), Heptest, anti-thrombin (aIIa) activity and anti-Xa (aXa) activity, the most pertinent parameter (from a biodynamic viewpoint) is plasma aXa activity. We demonstrated that dalteparin, nadroparin and enoxaparin exhibit statistically significantly different pharmacokinetic and overall disposition patterns. Normalized to the same injected dose (1,000 IU aXa), the relative actual amount of plasma anti-Xa activity generated by enoxaparin is 1.48 times greater (p < 0.001) than that of nadroparin and 2.28 times greater (p < 0.001) than that of dalteparin while the plasma amount induced by nadroparin is 1.54 times greater (p < 0.001) than that of dalteparin. The apparent total body clearance of enoxaparin doses (CL/F = 16.7 +/- 5.5 and 13.8 +/- 3.2 ml/min) is significantly smaller than those of nadroparin (CL/F = 21.4 +/- 7.0 ml/min; p < 0.01) and dalteparin (CL/F = 33.3 +/- 11.8 ml/min; p < 0.001) while dalteparin apparent clearance is about 1.5-fold greater (p < 0.001) than that of nadroparin. These LMMHs also differ by their renal excretion pattern: more fragments exhibiting an anti-Xa activity are recovered in urine following enoxaparin doses (6.4 and 8.7% of the dose, respectively) than following nadroparin (3.9%) and dalteparin (3.4%) injection. These differences in the disposition profiles explain why the apparent elimination half life t1/2 values of the LMMHs compared here are different: dalteparin: 2.8 h; nadroparin: 3.7 h; and enoxaparin: 4.1 h. Whether or not these differences may contribute to explain the different safety/efficacy balance of each of these antithrombotic medications remains to be discussed and needs further studies.
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PMID:Comparison of the pharmacokinetic profiles of three low molecular mass heparins--dalteparin, enoxaparin and nadroparin--administered subcutaneously in healthy volunteers (doses for prevention of thromboembolism). 749 71

Parnaparin is a low molecular weight (LMW) heparin which, like other members of its class, apparently demonstrates a greater antithrombotic effect relative to its anticoagulant activity when compared with the unfractionated heparin (heparin) from which it is derived. Moreover, subcutaneous parnaparin has a greater bioavailability and longer half-life than heparin, permitting once-daily administration for the prophylaxis of deep venous thrombosis (DVT) or the treatment of established vascular disorders. Prophylaxis with a 7-day regimen of parnaparin 3200 or 6400 IUaXa/day has consistently been associated with a lower incidence of confirmed DVT compared with usual prophylactic regimens of heparin. This intertreatment difference reached statistical significance in a large multicentre study involving a total of 610 surgical patients (3.2% for parnaparin vs 6.3% for heparin). Thus far, however, comparisons of parnaparin with other LMW heparins for this indication are unavailable. Parnaparin has demonstrated equivalent efficacy to heparin in the treatment of established vascular disorders, including phlebopathies and related syndromes, as well as peripheral arterial occlusive disease. Parnaparin also showed some benefit as an adjunctive therapy in patients with angina pectoris. The risk of general bleeding appears to be similar with parnaparin or heparin, although parnaparin results in fewer haematomas at the site of injection, partly because of the less frequent administration regimen. Parnaparin has also been associated with a lower incidence of pain and/or burning sensation at the injection site compared with heparin. As with other LMW heparins, the possibility that parnaparin will be infrequently associated with thrombocytopenia cannot be excluded. Thus, parnaparin may be preferred over traditional heparin for the prophylaxis of thromboembolic events in surgical patients (particularly those at high risk for DVT), as well as the treatment of established vascular disorders with a thrombotic aetiology. Compared with heparin, parnaparin offers the advantages of a more convenient administration regimen coupled with improved local tolerability. However, the therapeutic advantages of parnaparin relative to other LMW heparins have yet to be established in large scale comparative trials.
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PMID:Parnaparin. A review of its pharmacology, and clinical application in the prevention and treatment of thromboembolic and other vascular disorders. 751 62

The optimal administration regimens of low molecular weight heparins (LMWHs) have not yet been established. The aim of this study was to compare the efficacy and safety of 2500 and 5000 XaI units of the LMWH dalteparin in patients undergoing elective general surgery for malignant and benign abdominal disease. Prophylaxis was started in the evening before surgery and given once-daily every evening thereafter. The study was designed as a prospective, randomized, double-blind, multicentre trial. Some 66.4 per cent of patients were operated on for a malignant disorder. The primary endpoint was deep vein thrombosis (DVT) detected with the fibrinogen uptake test. Bleeding complications were recorded and classified. Analysis was made both on an intention to treat basis and in patients given correct prophylaxis (86.3 per cent). A total of 2097 patients were randomized and 27 excluded after randomization. A technically correct fibrinogen uptake test was obtained in 1957 patients. The incidence of DVT was significantly lower in patients given 5000 XaI units, this being true for both correct prophylaxis (6.8 versus 13.1 per cent, P < 0.001), on an intention to treat basis (6.6 versus 12.7 per cent, P < 0.001), and in patients with malignant disease (8.5 versus 14.9 per cent, P < 0.001). Sixty-seven patients (3.2 per cent) died within 30 days with no difference between the groups. There were two cases of fatal pulmonary embolism. The frequency of bleeding complications in the whole series was higher in patients randomized to 5000 XaI units (4.7 versus 2.7 per cent, P = 0.02), although this was not the case in those operated on for malignant disease (4.6 versus 3.6 per cent, P not significant). Dalteparin in the dose of 5000 XaI units started in the evening before surgery has a good thromboprophylactic effect in high-risk general surgery at the cost of a small bleeding risk. In patients with malignant disease there was no increased risk of bleeding. The overall frequency of fatal pulmonary embolism with dalteparin is extremely low, even in this high-risk group of patients.
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PMID:Low molecular weight heparin started before surgery as prophylaxis against deep vein thrombosis: 2500 versus 5000 XaI units in 2070 patients. 755 26

Reviparin is a low-molecular-weight heparin (LMWH) prepared by controlled nitrous acid digestion of porcine mucosal heparin. The trade name designation for this agent is Clivarin. This agent has been released in Germany and France for the prophylaxis of deep venous thrombosis (DVT) in surgical patients. This agent is developed utilizing optimized procedures and exhibits a uniform, narrow-molecular-weight distribution in comparison to the other commercially available LMWHs. The specific activity in the anticoagulant assays is approximated to be 32 U/mg whereas the specific activity in terms of anti-Xa units is designated 120 aXa U/mg. Reviparin is capable of producing a dose- and time-dependent antithrombotic effect in animal models of thrombosis. While the ex vivo effects are initially presented at antithrombotically active dosages, this agent has been found to produce antithrombotic effects without any detectable ex vivo actions. This agent is also known to release tissue factor pathway inhibitor (TFPI) after both intravenous (IV) and subcutaneous (SC) administration. Repeated administration of Reviparin produces progressively stronger antithrombotic effects. Similarly, the bleeding as measured by rabbit ear blood loss is also progressively increased. However, the ratio between the dosage producing these effects is quite large. The current studies are designed to provide additional data on the molecular profile using new calibration methods and additional results on the pharmacologic studies in a dose-dependent manner. In particular, the release of TFPI following IV and SC administration in a primate model is described. The effect of repeated administration mimicking the post-surgical prophylaxis of DVT is also reported in terms of any augmentation of the antithrombotic or hemorrhagic effects of these agents.
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PMID:Pharmacologic validation of the clinical effects of an optimized low-molecular-weight heparin-reviparin. 766 Jan 44

The levels of anti-IIa and anti-Xa activity, as reported in laboratory and clinical studies on low molecular weight heparin (LMWH) preparations, show a high degree of variability. This variation has been proposed as correlated to the variation in incidence of postoperative deep vein thrombosis (DVT) (8-30%) in different LMWH studies on comparable populations undergoing elective hip surgery. The aim of this study was to compare the ex vivo potency of Clexane (enoxaparin), Fragmin (dalteparin) and Logiparin (tinzaparin), applying the concept of bioequivalence, although unknown which activity/activities are best correlated to efficacy. Unfractionated heparin (UH) was included in the study as a reference drug. The drugs were studied with a cross-over technique in 12 healthy subjects and given subcutaneously in the doses recommended for orthopedic surgery. Blood samples were drawn each hour up to 10 h and at 12 h after administration. Anti-Xa and anti-IIa activities were measured using chromogenic substrate methods. The anti-Xa peak activity (Cmax) and the area under the curve (AUC) were highest for Clexane and Fragmin and lower for Logiparin and UH. Clexane and Fragmin were considered bioequivalent in anti-Xa activity. Regarding anti-IIa activity, no bioequivalence was found between the products. Fragmin was clearly different, with Cmax and AUC approximately twice as high as the other drugs. Whether the demonstrated differences in anti-Xa and anti-II activities are of any clinical significance remains unclear and can only be established by comparative clinical studies.
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PMID:A comparative study of three low-molecular weight heparins (LMWH) and unfractionated heparin (UH) in healthy volunteers. 766 22


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